Testosterone Tx May Ease Pain Perception

SAN FRANCISCO -- Men with chronic pain and opioid-induced androgen deficiency may find some pain relief with testosterone replacement therapy, a small trial suggested.

Although 14 weeks of testosterone did not affect the men's perception of their pain, which was the primary endpoint, the treatment significantly improved objective responses to painful stimuli in a laboratory setting, according to Shehzad Basaria, MD, of Brigham and Women's Hospital in Boston.

At the Endocrine Society meeting here, where Basaria presented the results, he said that the lack of clinical benefit accompanied by changes in objective responses is consistent with prior studies.

"When you look at pain studies with other analgesics, generally laboratory pain perception improves before a person feels that he is doing better," he said in an interview, adding that if the study had been longer, there may have been a significant clinical benefit.

A longer study is not currently planned, he said, because the analysis of additional measures in the current study -- sexual function, body composition, and metabolic parameters -- is ongoing.

"I would say that the practicing clinicians should not initiate testosterone therapy solely for the purpose of improving pain in these patients at this time," Basaria said. "The indications for testosterone replacement should be the same as they have been delineated in various guidelines by different organizations, such as [for] sexual dysfunction, decreased energy, and other related symptoms that patients have, which have been known to be correlated with low testosterone."

Androgen deficiency can be a problem in both men and women with chronic pain because opioids suppress the hypothalamic-pituitary-gonadal axis. In men, testosterone levels can be reduced to the castrated range.

The idea to use testosterone replacement therapy to improve pain perception and tolerance in men with opioid-induced androgen deficiency is supported by studies of castrated animals, which have shown that the administration of testosterone alleviates pain. Also, women are generally affected more than men by acute and chronic pain.

Basaria and colleagues tested the concept in a randomized trial that included 84 men, ages 18 to 64 (mean 49), who had chronic pain unrelated to cancer, had been taking an opioid analgesic for at least 4 weeks, and had a total testosterone level of less than 350 ng/dL at baseline (average 228 ng/dL). The average free testosterone level at baseline was 44 pg/mL. The group's mean body mass index was 33 kg/m2.

The men were randomized to 14 weeks of treatment with either 5 grams of transdermal testosterone gel or placebo. Two weeks after randomization, the testosterone dose was adjusted to achieve a serum testosterone concentration of 500 to 1,000 ng/dL.

Overall, 65 patients completed the study (36 in the testosterone group and 29 in the placebo group).

As expected, patients in the testosterone group had significant increases in total and free testosterone during the study (P<0.01), bringing both measures into the normal range.

Those changes, however, were not associated with any significant improvement on subjective pain perception measured using the Brief Pain Inventory at the end of the study (P=0.38).

Objective responses to pain were assessed using Quantitative Sensory Testing in the laboratory using mechanical, pressure, and cold stimuli, and those tests revealed some differences between the two groups.

Mechanical pain was assessed with 10 consecutive stimuli applied with a probe to the forearm. At the 10th stimulus -- when the patient would be feeling the most pain -- -- there was a significant improvement in pain tolerance in the testosterone group relative to the placebo group (P=0.05).

Cold tolerance was unaffected by treatment, but the pressure pain threshold was significantly improved in the testosterone group (P<0.05).

Quality of life, as measured on the Short Form-36 questionnaire, did not improve significantly with testosterone replacement, although there was a nonsignificant trend toward improvement on the domain of role limitation due to emotional problems (P=0.08).